Morel P, Reverdy C, Michel B, Ehrlich S D, Cassuto E
Génétique Microbienne, Institut National de la Recherche Agronomique, Domaine de Vilvert, 78352 Jouy en Josas Cedex, France.
Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10003-8. doi: 10.1073/pnas.95.17.10003.
Mutations affecting mismatch repair result in elevated frequencies of microsatellite length alteration in prokaryotes and eukaryotes. However, the finding that microsatellite instability is found often in cells with a functional mismatch repair system prompted a search for other factors of tract alteration. In the present report, we show that, in Escherichia coli, poly(AC/TG) tracts are destabilized by mutations that induce SOS. These observations may have implications for eukaryotic cells because recent results suggest the existence of a mammalian SOS response analogous to that in prokaryotes. In addition, a defect in the 5'-3' exonuclease domain of DNA polymerase I, homologous to the mammalian FEN1 and the yeast RAD27 nucleases, leads to a marked increase in repeat expansions characteristic of several genetic disorders. Finally, we found that the combination of a proofreading defect with mismatch repair deficiency results in extreme microsatellite instability.
影响错配修复的突变会导致原核生物和真核生物中微卫星长度改变的频率升高。然而，在具有功能性错配修复系统的细胞中经常发现微卫星不稳定性这一发现促使人们寻找导致序列改变的其他因素。在本报告中，我们表明，在大肠杆菌中，诱导SOS的突变会使聚（AC/TG）序列不稳定。这些观察结果可能对真核细胞有影响，因为最近的结果表明存在类似于原核生物的哺乳动物SOS反应。此外，与哺乳动物FEN1和酵母RAD27核酸酶同源的DNA聚合酶I的5'-3'核酸外切酶结构域缺陷会导致几种遗传疾病特有的重复序列扩增显著增加。最后，我们发现校对缺陷与错配修复缺陷相结合会导致极端的微卫星不稳定性。
